Technical Abstract:
Fructose (FRU) constitutes an important source of carbohydrate intake. FRU is absorbed into the portal circulation unchanged and totally extracted by the liver on a first-pass basis. Evidence exists for the direct conversion of FRU into glucose (GLU) (Proc. Natl. Acad. Sci. USA, Vol. 87, pp 5449, 1990). The current study was undertaken to determine the contribution of FRU (both 6 and 3 carbon units) to GLU formation during meal ingestion. Following an overnight fast, three healthy adults (age, 25+/-4(SE) yrs; 60.7+/-3.2 kg.; BMI, 22.6+/-0.7 kg/m2) received a bolus of oral FRU (0.72 g/kg) enriched with 2 percent [U-13C] FRU (Study 1) or oral FRU (0.72g/kg) enriched with 2 percent [U-13C] FRU plus GLU (0.72 g/kg) (Study 2). Four hours following meal ingestion, subjects received I.V. bolus of glucagon (15ug/kg) to assess the uptake and storage of fructose carbons in glycogen. Glucose production rate (GPR, measured with [6,62H2] glucose) at baseline and GLU plasma enrichments of E[13C3]GLU and E[13C6]GLU were measured. Results: Study 1: GPR was 12.1+/-1.5 µmol.kg-1.min-1, and E[13C3]GLU at 1,2,3, and 4h after bolus were 1.8+/-0.3, 2.3+/-0.08, 2.4+/-0.1, and 1.8+/-0.2 percent, respectively. Study 2: GPR was 10.9+/-0.8 µmol.kg-1.min-1, and E[13C3]GLU at 1,2,3, and 4 after bolus were 0.48+/-0.03, 0.64+/-0.01, 0.82+/-0.02, and 1.02+/-0.09 percent, respectively. Following glucagon administration, the area under the curve (AUC) for the difference in plasma glucose concentration (mM) at 10, 20, 30, 45, and 60 minutes was 81+/-37 for fructose alone; and 79+/-24 for fructose with glucose (p=0.96); while the AUC for the difference in E[13C3]GLU at 10, 20, 30, 45, and 60 minutes was -16+/-5 for FRU alone, and 7.5+/-3 for FRU with GLU (p =0.01). The enrichment values for E[13C6]GLU were essentially zero (<0.1 percent) in both studies. Conclusions: 1) There is no direct conversion from fructose to glucose. 2) During ingestion of fructose alone up to 60 percent of glucose is derived from 3 carbon fractions of fructose, but only 20 percent during fructose plus glucose. 3) A greater fraction of fructose was converted to glycogen when fructose is co-ingested with glucose compared to fructose alone.